Child Sexual Abuse (CSA) is one of the strongest and most consistent predictors of adolescent problems. Youth who have experienced CSA are at significant risk for early initiation, use, and abuse of substances. For example. research has indicated that adolescent CSA victims are over 3.5 times more likely to report marijuana abuse/dependence compared to non-CSA victims. Other negative sequelae, such as posttraumatic stress disorder (PTSD) and HIV sexual risk behaviors, also have been clearly linked with CSA. Remarkably, no behavioral interventions have been developed and rigorously evaluated for this population that: a) take an integrated approach to targeting such sequelae through use of existing empirically supported interventions; and b) incorporate risk reduction for less symptomatic youth. Risk reduction and treatment tailored to adolescent CSA victims, which addresses the individual, family, and community risk and resiliency factors for adolescent substance use problems and incorporates exposure-based treatment for PTSD symptoms, as well as evidence based prevention interventions for HIV-related sexual behaviors, and is warranted. Risk Reduction through Family Therapy (RRFT) has been developed by the PI, a NIDA-K awardee (K23DA018686) and Early Stage Investigator, for this purpose. Preliminary findings from a Stage 1a feasibility trial and a Stage 1b pilot randomized controlled trial (RCT) are promising, indicating that RRFT can be readily learned and implemented with fidelity, and that it can lead to improvements in drug use and drug use-related risk and protective factors, PTSD symptoms, and HIV sexual risk behaviors (Danielson et al., 2010). In following NIDA's recommended stage model of behavioral therapy development, the overall goal of this application is to conduct a Stage II RCT to more rigorously evaluate the efficacy of RRFT (vs. Treatment As Usual) from pre-treatment through 18 months. The first specific aim of the proposed study is to evaluate the efficacy of RRFT in reducing substance use problems and prognostic factors among CSA victims experiencing trauma-related symptoms. The second specific aim is to evaluate the efficacy of RRFT in reducing PTSD and HIV sexual risk behaviors among this population. In order to better make maximum use of the data from this proposed efficacy trial and to inform potential next steps in this line of treatment research (per NOT-DA-019), preliminary investigation on mechanisms of action in RRFT also will be pursued as an exploratory aim. Specifically, intermediate targets of RRFT, such as parenting practices and emotional reactivity, as putative mechanisms of action for improvements in substance use and PTSD and risky sexual behaviors will be explored. The results of the proposed study will have a significant impact on public health by informing intervention efforts for the multifaceted clinical needs of adolescent CSA victims, who are at high risk for drug use, HIV infection, other problems in adolescence and adulthood. Demonstrating the efficacy of this promising risk reduction and treatment approach could provide a valuable clinical tool for community-based therapists.